This encapsulation is intended to protect the active substance and then to allow its release in a controlled manner, especially into an aqueous medium.
Silicone polymers have been employed for a long time in encapsulating coatings for active substances, and silicone polymers have two properties that are of value in applications of this type, namely their biocompatibility and their permeability to gases and to small molecules.
Silicones are generally employed in the form of macromolecules bearing reactive chemical functional groups which are crosslinked at the surface of the active substance to form a coating which is made up of crosslinked polymers that are insoluble in common organic solvents. This state of the art is illustrated by patents EP-A-267,003, EP-A-280,400 and U.S. Pat. No. 4,370,160.
According to this art, the crosslinking of these silicone polymers takes place in the presence of the active substance. This crosslinking is generally carried out using an organometallic curing catalyst, by heating or by irradiation (with ultraviolet, infrared, electron beam, gamma) or a combination of these means. Since this crosslinking involves chemical or photochemical reactions in the presence of the active substance, it can therefore have a detrimental effect on this active substance.
Furthermore, the intrinsic physicochemical properties of the active substance may interfere with or even completely inhibit the crosslinking process, and this problem is particularly severe when the active substance contains a thiol functional group.
In addition, the biocompatible nature of the polymer is of crucial importance in pharmaceutical and biological applications. It is difficult to remove from the polymer used to encapsulate an active substance undesirable products such as catalysts and residual polymers which are not integrated into the crosslinked material.
At the present time, the process of encapsulation by successive film-coating, which is the most effective from the technical standpoint for producing the encapsulation of active substances, comprises at least one stage of spraying a film-forming composition containing an organic polymer in solution in an organic solvent or in the form of an aqueous emulsion or dispersion followed by at least one drying operation, that is to say evaporation of the organic solvent and/or water.
An example of a process of this kind is the process known by the name of "spray coating", according to which the particles to be encapsulated are stirred (fluidized) by a gas stream which also ensures their drying, that is to say the evaporation of the organic solvent and/or water.
The film-forming composition is sprayed by one or more nozzles situated in various regions of the reactor depending on the process type employed, for example, above, within or at the base of the cloud of particles.
Thus, this spraying is at the base of the fluidized bed of particles in the Wurster process. The Wurster spraying technique is described in detail in patents U.S. Pat. Nos. 2,799,241, 3,089,824, 3,117,027, 3,196,827, 3,207,824, 3,241,520, 3,253,994 and EP-A-188,953.
In order to use the valuable physico-chemical properties of silicones in the spraying/drying process without having the disadvantages of crosslinked materials, a person skilled in the art may be inclined to think of employing oily or resinous diorganopolysiloxane polymers which are not crosslinkable, that is to say unreactive in a film-coating process using spraying/drying of particles of active substances.
Unfortunately, as is demonstrated in the comparative examples of the present application, these unreactive silicone oils or resins are particularly unsuited for implementing the process of encapsulation using spraying/drying.
In fact, during the encapsulation process, and consequently even more at the end of the process, the encapsulated particle has a marked tendency to agglomeration due to the adhesive and sticky nature of the silicone polymer. Moreover, even in the absence of the adhesive nature, the silicone coating tends to creep and the particle is no longer perfectly encapsulated.
In the process of the present invention a class of polymer is employed for encapsulating particles of active substance which has the same advantages as the known silicone polymers, but without disadvantages of capsules of crosslinked silicone polymers and the disadvantages of capsules of unreactive silicone polymers.